Role of the Blood-Brain barrier (BBB) in Stroke and Dementia, and Other Ageing Related Brain Conditions

PhD Scholarship

Irregular and rapid heartbeat can lead to cardiovascular disease, including heart failure, blood clots and stroke, affecting millions of people worldwide. Recent evidence suggests a link between cardiovascular disease and brain injury, most likely due to disrupted blood-brain barrier (BBB, the physiological barrier that protects the brain from blood-borne toxins and pathogens, and regulates molecular traffic between the blood and the brain). Maintaining normal blood flow is essential for brain endothelial function, including maintaining barrier integrity. We have shown that microvessicles (MVs, small membraneous vesicles released by cells) are released from brain endothelial cells during inflammatory conditions leading to barrier dysfunction. We hypothesise that MVs released during conditions with altered blood flow or sheer stress will lead to disruption of the BBB and worsening of outcomes. The aim of this project is to investigate the underlying mechanisms with a focus on the BBB.

All tissues in the body are isolated, to varying degrees, from their respective blood supplies by blood-tissue barriers. The brain is no exception and the blood-brain barrier (BBB) is considered the least ‘leaky’ barrier in the body. BBB ’tightness’ is necessary to maintain the ionic milieu to allow appropriate function of the billions of neurons that inhabit the brain. BBB integrity is also critical to keep potentially invasive blood borne immune cells out of the brain. The autoimmune condition multiple sclerosis is an example of the damage that can be done when immune cells gain access to the brain. Stroke and dementia are also associated with loss of BBB integrity, but what causes this loss remains poorly understood.

The major aim of this PhD project is to understand the mechanisms of BBB breakdown. We have previously shown that microvesicles (MVs, small membraneous vesicles released by cells) are released from the brain endothelial cells that line blood vessels, during inflammatory conditions leading to barrier dysfunction. We hypothesise that MVs released during conditions with altered blood flow, such as with stroke, or with the neuroinflammation associated with dementia and other ageing related brain conditions, will lead to disruption of the BBB and worsening of outcomes.

Eligibility Criteria

In addition to the minimum eligibility criteria, we are seeking domestic students with Honours (1 or 2A) or equivalent, or a Master's degree with a background in biomedical sciences, biology or biochemistry are encouraged to apply.The successful applicant must be able to commence their PhD by 15th December 2019.

Application Procedure

Interested applicants should send an email expressing their interest along with scanned copies of their academic transcripts, CV, a brief statement of their research interests and a proposal that specifically links them to the research project.